EMD-34314

Single-particle
2.72 Å
EMD-34314 Deposition: 17/09/2022
Map released: 28/02/2024
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-34314

SARS-CoV-2 RNA E-RTC complex with RMP-nsp9 and GMPPNP

EMD-34314

Single-particle
2.72 Å
EMD-34314 Deposition: 17/09/2022
Map released: 28/02/2024
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Severe acute respiratory syndrome coronavirus 2
Sample: E-RTC_RMP-nsp9_GMPPNP
Fitted models: 8gwk (Avg. Q-score: 0.423)

Deposition Authors: Yan LM, Huang YC, Ge J, Liu ZY, Gao Y, Rao ZH, Lou ZY
A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors.
Yan L, Huang Y, Ge J, Liu Z, Lu P , Huang B, Gao S, Wang J, Tan L, Ye S, Yu F, Lan W, Xu S, Zhou F, Shi L, Guddat LW, Gao Y, Rao Z, Lou Z
(2022) Cell , 185 , 4347 - 4360.e17
PUBMED: 36335936
DOI: doi:10.1016/j.cell.2022.09.037
ISSN: 1097-4172
Abstract:
Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5' end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown "Nuc-pocket" in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an "induce-and-lock" mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs.